Analysis of Efficacy and Costs of Antifungal Prophylaxis in Patients Undergoing Chemotherapy for Acute Leukemia: “Real Life” Evaluation

Antifungal prophylaxis (AP) and therapy (AT) are increasing the costs during treatment for acute myeloid leukemia (AML). Efficacy of AP, empirical (EMP) and diagnostic tool led pre-emptive (PRE) AT still need to be evaluated and improved.

In 2010 we performed a prospective study analysing all consecutive patients (pts) treated for AML in terms of AP/AT, choice and costs of the applied diagnostic procedures and EMP or PRE AT. All pts received regular lung CT scans, Galactomannan (Gal) and ß D-glucan (ß-D) tests. AP switched every three months between posaconazole (P) and fluconazole (F) to evaluate P-prophylaxis. Planned EMP consisted mainly of liposomal Amphotericin (LAMB) 1 mg/kg and planned PRE of LAMB 3 mg/kg.

In 37 pts. 86 cycles (cs) of induction (IND; n=51)/consolidation (CONS; n=35) chemotherapy have been documented. F 200mg/d as AP was given in 46 and P 600mg/d in 40 cs. EMP or PRE was initiated in 9+9 /46 cs (IND n=14; CONS n=4) of F (39%) and in 8+9 / 40 cs of P (42.5%; p=n.s.) (IND n=14; CONS n=3); EMP/PRE AT consisted mainly of LAMB 1 (n=12) or LAMB 3 (n=17) with no further antifungal drug escalation in 26/29 cs (89.6%); in 4 cs toxicity led to modification after 10 days in median of LAMB. 23/121 CT scans (19%; 119€ each), 31/277 ß-D (11%; 55€ each) and 13 / 440 GAL tests (3 %; 9€ each) were positive resulting in mean diagnostic costs of 372 €/c. In only 5/86 cs (6%) all 3 and in 7/86 cs (8%) 2 procedures showed positive results simultaneously. No proven, 10 probable (P and F AP: n=5 each) and 7 possible fungal infections (P n=5; F n=2) were detected. No patient died due to IFI, 3/37 pts. due to AML and none experienced > grade 3 toxicity by antifungal therapy.

Recommended posaconazole AP showed no advantage compared to F but strikingly higher expenses (mean cost 2438 € vs. 24 €/c). LAMB as primary AT showed very convincing clinical results. These results underline that clinical signs/judgement and CT scan are still the leading, inexpensive decision tools for starting AT. Our consequences are stop of P as AP and of regular GAL/ß-D testing. This project is supported with a grant by GILEAD.

Bertz:MSD: Membership on an entity's Board of Directors or advisory committees; GILEAD: Research Funding.